• Clinical and Experimental Reproductive Medicine
• /
• v.42 no.2
• /
• pp.72-76
• /
• 2015

$17{\alpha}$-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In $17{\alpha}$-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with $17{\alpha}$-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with $17{\alpha}$-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with $17{\alpha}$-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.24 no.1
• /
• pp.37-42
• /
• 2024

Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by decreased cortisol secretion, with 21-hydroxylase deficiency being the most common type. It is uncommon for CAH to present primarily as cholestasis; therefore, when a patient presents with prolonged jaundice, it is difficult to suspect CAH immediately. In this report, we aim to share our experience with an exceptional case of 21-hydroxylase deficiency. A 28-day-old male visited the outpatient clinic due to prolonged jaundice and elevated 17α-hydroxyprogesterone (17-OHP) levels in the newborn screening test. Since he showed no other symptoms such as lethargy or vomiting, he underwent a routine blood test for jaundice and a retest of 17-OHP at the outpatient clinic. Two hours after the blood draw, he was found to have severe hyponatremia and hyperkalemia, so he was immediately admitted to the intensive care unit. After treatment with hydrocortisone, fludrocortisone, sodium chloride, and intravenous fluids, the cholestasis and electrolyte imbalances improved over time. He was diagnosed with 21-hydroxylase deficiency, salt-wasting type, which was confirmed by the ACTH stimulation test and genetic testing. It is important to make a prompt diagnosis of CAH to avoid missing critical timing. Therefore, CAH should not be overlooked, even if the patient does not exhibit typical symptoms.

• Clinical and Experimental Pediatrics
• /
• v.60 no.2
• /
• pp.31-37
• /
• 2017

Steroid 21-hydroxylase deficiency is the most prevalent form of congenital adrenal hyperplasia (CAH), accounting for approximately 95% of cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, tumor, osteoporosis, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and health-care providers. Psychosocial issues frequently affect adherence to glucocorticoid treatment. Therefore, the safe transition of adolescents to adult care requires regular follow-up of patients by a multidisciplinary team including pediatric and adult endocrinologists. The major goals for management of adults with 21-hydroxylase deficiency are to minimize the long-term complications of glucocorticoid therapy, reduce hyperandrogenism, prevent adrenal or testicular adrenal rest tumors, maintain fertility, and improve quality of life. Optimized medical or surgical treatment strategies should be developed through coordinated care, both during transition periods and throughout patients' lifetimes. This review will summarize current knowledge on the management of adults with CAH, and suggested appropriate approaches to the transition from pediatric to adult care.

• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.16 no.2
• /
• pp.70-78
• /
• 2016

21-hydroxylase deficiency (21-OHD), most common form of congenial adrenal hyperplasia, is categorized into classical forms, including the salt-wasting (SW) and the simple virilizing (SV) types, and nonclassical (NC) forms based on the severity of the disease. Newborn screening for 21-OHD has been performed in Korea since 2006. $17{\alpha}$-hydroxyprogesterone (17-OHP) is a marker for 21-OHD and is measured using a radioimmunoassay or a fluoroimmunoassay. Premature and low birth weight infants are likely to give false positive 17-OHP findings, therefore, cutoff values for these infants should be determined based on gestational weeks or birth weight. ACTH simulation test is helpful when the 17-OHP shows equivocal increase, and it is gold standard for diagnosis of NC type. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Molecular analysis of CYP21A2 is useful for confirming diagnosis of mild SV or NC type, predicting prognoses, and genetic counseling. In order to make newborn screening for 21-OHD more efficient, early detection of boy with SW type, early determination of girl with ambiguous genitalia, detection of NC type, and overcoming of false positive in premature and low birth weight infants should be considered. Above all, early treatment should be started when the patient is suspected as having 21- OHD clinically before confirming the diagnosis to prevent adrenal crisis. Here, author reviewed recent articles of guideline and proposed guideline for 21-OHD.

• Clinical and Experimental Pediatrics
• /
• v.51 no.9
• /
• pp.1018-1022
• /
• 2008

Testicular adrenal rest tumors are a well-known complication in male patients with congenital adrenal hyperplasia. Corticosteroid suppressive therapy usually results in the regression of these tumors. We describe a patient with 21-hydroxylase deficiency who developed bilateral testicular masses. Despite steroid suppressive therapy, the tumors did not regress and hormonal control was poor. Consequently, bilateral partial orchiectomies were performed.

• Journal of Genetic Medicine
• /
• v.1 no.1
• /
• pp.27-31
• /
• 1997

Steroid 21 hydroxylase deficiency is a major cause of congenital adrenal hyperplasia (CAH) and is caused by genetic impairment of the gene (CYP21B). In the human genome, CYP21B is located within the MHC class III region on the short arm of chromosome 6. Most of the genes in this region are highly polymorphic and crowded. Also the CYP21B gene is accompanied by its pseudogene (CYP21A) and tandemly arranged with two genes of fourth component of complement. This highly complex gene cluster in this area may predispose genetic instability of CYP21, i.e. mutations. In this study, tried to investigate the frequency of duplication and deletion of CYP21 and patterns of the genetic alterations of these genes.We also compared the genetic alteration in normal subjects with those of the CAH patients. The results showed that 15% of the normal korean population have duplication or deletion of CYP21. There was one normal subject with heterozygous deletion of CYP21B. Of the 5 CAH patients examined, 2 were found to show abnormal patterns. One was a large-scale gene conversion and the other a gene conversion associated with deletion involving both CYP21B and C4 locus II gene. Through this study, we carne to the conclusion that the duplication or even deletion of CYP21 and C4 might be quite a common event in the Korean population and these rearrangements must be regarded as polymorphisms. It could contribute to a high incidencs of CAH by providing a genetic pool of instable CYP21.

• Analytical Science and Technology
• /
• v.32 no.6
• /
• pp.225-232
• /
• 2019

Traceability establishment in chemical measurements is a like a linkage established through an unbroken chain from the measured results to the international system (SI) of units. The primary process for traceability establishment is the purity assignment of a target material to be measured. In this study, we studied the purity assignment of 17α-hydroxyprogesterone (17-OHP). The presence of 17-OHP is indicative of congenital adrenal hyperplasia (CAH) and it builds up due to the deficiency of 21-hydroxylase and 11β-hydroxylase enzyme in the human blood. The purity assignment of 17-OHP was performed by the mass balance method, in which the impurities are categorized into four classes: total related structural impurities, water, residual organic solvents, and nonvolatiles/inorganics. The total related structural impurities were characterized by HPLC-UV; water content was determined by Karl-Fisher coulometer; and the total residual solvents and nonvolatiles/inorganics were determined by TGA. The purity of 17-OHP from a commercial manufacturer was calculated as 993.30 mg/g, and the expanded uncertainty was 0.58 mg/g. The proposed method was validated by uncertainty evaluation and comparing with the actual value of purity.

• Clinical and Experimental Pediatrics
• /
• v.54 no.5
• /
• pp.224-227
• /
• 2011

A sclerosing stromal tumor of the ovary is an extremely rare benign tumor; it usually is found during the second and third decades of life. Patients present with pelvic pain or a palpable abdominal mass. Hormonal effects such as masculinization are uncommon. Here, an 11-year old premenarchal girl presented with deepening of the voice. In addition, clitoromegaly and hirsutism with a male suprapubic hair pattern were observed. The laboratory findings showed that the testosterone level was elevated to 3.67 ng/ml, andostenedione to above 10 ng/ml, dehydroepiandrosterone-sulfate to 346 ${\mu}g$/dl and 17-hydroxy progesterone (17-OHP) to 11.28 ng/ml. The chromosome evaluation revealed a 46,XX female karyotype. An adrenocorticotropic hormone stimulation test was performed. The 17-OHP to cortisol ratio in 30 minutes was 0.045, which suggested a heterozygote for the 21-hydroxylase deficiency. However, the CYP21A2 gene encoding steroid 21-hydroxylase showed normal. The pelvic ultrasound showed a heterogeneous mass consisting of predominantly solid tissue in the pelvic cavity. The pelvic magnetic resonance imaging revealed an $8.9{\times}6.2{\times}6.6$ cm mass of the left ovary. A left oophrectomy was performed and microscopic examination confirmed a sclerosing stromal tumor. Immunohistochemical studies showed that the tumor was positive for smooth muscle actin and vimentin, but negative for S-100 protein and cytokeratin. Following surgery, the hormone levels returned to the normal range and the hirsutism resolved.

• Clinical and Experimental Pediatrics
• /
• v.50 no.3
• /
• pp.302-305
• /
• 2007

As a result of the widespread use and enhanced quality of high-resolution radiological techniques, a recent report has revealed a relatively high prevalence of small adrenal tumors in patients with untreated congenital adrenal hyperplasia due to 21-hydroxylase deficiency. However, there are scarcely any pediatric cases of adrenocortical tumor following long-term treatment in patients suffering with congenital adrenal hyperplasia. We report here on a pediatric female case of adrenocortical adenoma despite adequate long-term treatment for the salt-losing type of congenital adrenal hyperplasia.

• Clinical and Experimental Pediatrics
• /
• v.54 no.3
• /
• pp.137-140
• /
• 2011

Testicular adrenal rest tumors (TARTs) are considered to be formed from aberrant adrenal tissue that has become hyperplastic because of elevated adrenocorticotropic hormone (ACTH) in male patients with congenital adrenal hyperplasia (CAH). A 6-year-old boy presented with testicular enlargement and pubic hair. He was diagnosed with CAH complicated by precocious puberty. However, he was not followed-up. At the age of 17, he visited the outpatient clinic because of testicular enlargement and short stature. His right and left testicles were $10{\times}6$ cm and $7.5{\times}4.5$ cm, respectively. His height was 155.1 cm (standard deviation score (SDS), -2.90). The diagnosis of CAH due to 21 hydroxylase deficiency was confirmed by mutation analysis of CYP21A2. Histological examination of the testes showed large, polygonal, eosinophilic cells with round nuclei and prominent nucleoli, which were suggestive of TARTs. He was treated with dexamethasone for 3 weeks and tumors regressed. Subsequently, dexamethasone was replaced by prednisolone and $9{\alpha}$-fludrocortisone; thereafter, the reduced testis size has been maintained.